HPC5_2020

19 HPC Today SKIN CARE ferrugineum , also called alpine rose, leaves and its senolytic effect on human fibroblasts. Moreover, an improvement of skin redness and elasticity was observed in a placebo-controlled, randomized clinical study. MATERIALS AND METHODS Senolytic assay In order to distinguish between the prevention of senescence and true senolytic activity, Normal Human Dermal Fibroblasts were first stressed with 500 µM H 2 O 2 for 2 hours to induce premature senescence through oxidative stress. The medium was then exchanged, and the cells were grown for 3 days to fully establish the senescent phenotype in a subpopulation of the cells. This mixture of senescent and healthy fibroblasts was then treated for 48 hours with either 1% alpine rose extract or Navitoclax (Cayman Chemical, Ann Arbor, USA), a known senolytic drug, or not treated (control). Following fixation with 2% formaldehyde and 0.2% glutaraldehyde, cells were stained with DAPI and the relative total cell number was determined by fluorescence measurement. Senescence- associated β-galactosidase activity assay was performed according to (12) and a total of 400 cells were counted. Counting the β-gal-positive cells as amarker for senescence and calculating the percentage compared to the total cell number revealed the treatment efficacy. Clinical anti-aging study In a double-blind, placebo- controlled clinical study, forty- four Caucasian women aged between 40 and 65 years (mean age: 55 years) with redness on the cheeks were split into two groups. One group applied a creamwith 2% alpine rose extract and the other group applied the corresponding placebo cream on the entire face and neck twice daily for 28 days. Skin color was measured using a Spectrocolorimeter CM700-d (Konica Minolta, Japan) and skin elasticity was determined with a Cutometer MPA 580 (Courage + Khazaka, Germany). In addition, extracellular matrix degradation is promoted, which leads to a lack of skin elasticity and sagging. It is therefore important to keep the senescent cell population under control. How to combat “zombie cells”? There are several options to deal with senescent cells. The first is prevention: when the damage that leads to senescence is repaired, the cells would not turn senescent. However, this is not possible for all damage occurring in the cells, as our body, and especially the skin, is constantly exposed to internal and external stressors. Another option would be to prevent senescence from happening despite the damage. This would prove harmful for the tissue as cells dividing with extensive DNA damage and passing these errors onto their daughter cells should be avoided at all costs as it could lead to uncontrolled cell growth. The third option, which has become a highly promising anti-aging therapy in the past few years, is to eliminate senescent cells in a targeted way so that the surrounding healthy cells are not affected. This novel concept known as “senolytics” helps to clear tissues of senescent cells in order to reduce inflammation and rejuvenate the tissue. The term senolytics was coined in 2015 by researchers from the Mayo Clinic and the Scripps research institute in the USA, who described a mechanism through which senescent cells are selectively eliminated without harming healthy dividing cells (10). The targeted senescent cells are going into apoptosis and are subsequently cleared from the tissue. Clearing senescent cells both reduces negative effects of aging pathologies and extends median lifespan (11). Despite being a brand-new life science topic, there have already been more than 300 scientific publications that investigate the senolytic activity of numerous compounds. So far, the concept of senolytics has not yet been applied in the cosmetic field despite its great potential for skin rejuvenation. Here we describe an extract of organic rhododendron Figure 1. Schematic representation of a senescent fibroblast in the dermis. Secretion of cytokines by these senescent cells leads to constant inflammation in the skin, which results in collagen degradation and accelerated skin aging. Figure 2. Schematic representation of the senolytic study concept. The desired senolytic activity depicted on the right results in the depletion of senescent cells while not affecting the healthy cell number. Figure 3. The alpine rose extract exhibits senolytic activity. Cell numbers of senescent and non-senescent cells are shown normalized to control cells in which senescence was induced with hydrogen peroxide. vol. 15(5) 2020

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